A T Cell Receptor Locus Harbors a Malaria-Specific Immune Response Gene.
Immunity
; 47(5): 835-847.e4, 2017 11 21.
Article
in En
| MEDLINE
| ID: mdl-29150238
ABSTRACT
Immune response (Ir) genes, originally proposed by Baruj Benacerraf to explain differential antigen-specific responses in animal models, have become synonymous with the major histocompatibility complex (MHC). We discovered a non-MHC-linked Ir gene in a T cell receptor (TCR) locus that was required for CD8+ T cell responses to the Plasmodium berghei GAP5040-48 epitope in mice expressing the MHC class I allele H-2Db. GAP5040-48-specific CD8+ T cell responses emerged from a very large pool of naive Vß8.1+ precursors, which dictated susceptibility to cerebral malaria and conferred protection against recombinant Listeria monocytogenes infection. Structural analysis of a prototypical Vß8.1+ TCR-H-2Db-GAP5040-48 ternary complex revealed that germline-encoded complementarity-determining region 1ß residues present exclusively in the Vß8.1 segment mediated essential interactions with the GAP5040-48 peptide. Collectively, these findings demonstrated that Vß8.1 functioned as an Ir gene that was indispensable for immune reactivity against the malaria GAP5040-48 epitope.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Plasmodium berghei
/
Receptors, Antigen, T-Cell
/
Protozoan Proteins
/
Histocompatibility Antigen H-2D
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Immunity
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2017
Type:
Article
Affiliation country:
United States